Specific Host Defenses: The Immune Response

The Immune Response Immune Response: Third line of defense. Involves production of antibodies and generation of specialized lymphocytes against specific antigens.

The Immune Response is the Third Line of Defense Against Infection

Adaptive (Acquired ) Immunity: Humoral Immunity Humoral Immunity (Antibody mediated response) (Antibody mediated response) Cellular Mediated Immunity (CMI Cellular Mediated Immunity (CMI (T- cell mediated immunity) (T- cell mediated immunity)

Acquired Immunity : Immunity that an organism develops during lifetime. Immunity that an organism develops during lifetime. u Not genetically determined. u May be acquired naturally or artificially. F Development of immunity to measles in response to infection or vaccination.

Characters Of Acquired Immune Response 1) Highly specific for the invading organism 2) Discrimination between “self and “non self” molecules The response only occurs to “non self” molecules The response only occurs to “non self” molecules 3) Diversity: - It can respond to millions of different antigens - It can respond to millions of different antigens - Lymphoctes population consists of many different clones - Lymphoctes population consists of many different clones - Each clone express an antigen receptor and responds - Each clone express an antigen receptor and responds only to one antigenic epitope only to one antigenic epitope

Mechanism Of Acquired Immune Response Acquired immune response is initiated by: Acquired immune response is initiated by: * Recognition of the antigen by specific lymphocytes * Activation of these specific lymphocytes * Proliferation and differentiation into effector cells; -The effector cells eliminate the antigen -The effector cells eliminate the antigen - Return of homeostasis and development of memory cells - Return of homeostasis and development of memory cells - Memory cells evoke a more rapid and long response on - Memory cells evoke a more rapid and long response on re-exposure to same antigen re-exposure to same antigen

Types of Acquired Immunity I. Naturally Acquired Immunity: Obtained in the course of daily life. A. Naturally Acquired Active Immunity: u Antigens or pathogens enter body naturally. u Body generates an immune response to antigens. u Immunity may be lifelong (chickenpox or mumps) or temporary (influenza or intestinal infections). B. Naturally Acquired Passive Immunity: u Antibodies pass from mother to fetus via placenta or breast feeding (colostrum). u No immune response to antigens. u Immunity is usually short-lived (weeks to months). u Protection until child’s immune system develops.

Types of Acquired Immunity (Continued) II. Artificially Acquired Immunity: Obtained by receiving a vaccine or immune serum. 1. Artificially Acquired Active Immunity: u Antigens are introduced in vaccines (immunization). u Body generates an immune response to antigens. u Immunity can be lifelong (oral polio vaccine) or temporary (tetanus toxoid). 2. Artificially Acquired Passive Immunity: u Preformed antibodies (antiserum) are introduced into body by injection. F Snake antivenom injection from horses or rabbits. u Immunity is short lived (half life three weeks). u Host immune system does not respond to antigens.

Humoral (Antibody-Mediated) Immunity u Involves production of antibodies against foreign antigens. u Antibodies are produced by a subset of lymphocytes called B cells. u B cells that are stimulated will actively secrete antibodies and are called plasma cells. u Antibodies are found in extracellular fluids (blood plasma, lymph, mucus, etc.) and the surface of B cells. u Defense against bacteria, bacterial toxins, and viruses that circulate freely in body fluids, before they enter cells. u Also cause certain reactions against transplanted tissue.

Antibodies are Produced by B Lymphocytes

Humoral Immune Response

Antigens Antigen: Molecules from a pathogen or foreign organism that provoke a specific immune response.

Antigens u Most are proteins or large polysaccharides from a foreign organism. u Microbes: Capsules, cell walls, toxins, viral capsids, flagella, etc. u Nonmicrobes: Pollen, egg white, red blood cell surface molecules, serum proteins, and surface molecules from transplanted tissue. u Lipids and nucleic acids are only antigenic when combined with proteins or polysaccharides. u Molecular weight of 10,000 or higher.

Antigens Epitope: u Small part of an antigen that interacts with an antibody. u Any given antigen may have several epitopes. u Each epitope is recognized by a different antibody.

Epitopes: Antigen Regions that Interact with Antibodies

Antibodies u Proteins that recognize and bind to a particular antigen with very high specificity. u Made in response to exposure to the antigen. u One virus or microbe may have several antigenic determinant sites, to which different antibodies may bind. u Each antibody has at least two identical sites that bind antigen: Antigen binding sites. u Valence of an antibody: Number of antigen binding sites. Most are bivalent. u Belong to a group of serum proteins called immunoglobulins (Igs).

Antibody Structure u Monomer: A flexible Y-shaped molecule with four protein chains: u 2 identical light chains u 2 identical heavy chains u Variable Regions: Two sections at the end of Y’s arms. Contain the antigen binding sites (Fab). Identical on the same antibody, but vary from one antibody to another. u Constant Regions: Stem of monomer and lower parts of Y arms. u Fc region: Stem of monomer only. Important because they can bind to complement or cells.

Basic Antibody Structure n Two identical heavy chains u Gamma u Delta u Alpha u Mu u Epsilon

Basic Antibody Structure n Two identical light chains u Kappa OR u Lambda

Antibody Structure

Immunoglobulin Classes I. IgG u Structure: Monomer u Percentage serum antibodies: 80% u Location: Blood, lymph, intestine u Half-life in serum: 23 days u Complement Fixation: Yes u Placental Transfer: Yes u Known Functions: Enhances phagocytosis, neutralizes toxins and viruses, protects fetus and newborn.

Immunoglobulin Classes II. IgM u Structure: Pentamer u Percentage serum antibodies: 5-10% u Location: Blood, lymph, B cell surface (monomer) u Half-life in serum: 5 days u Complement Fixation: Yes u Placental Transfer: No u Known Functions: First antibodies produced during an infection. Effective against microbes and agglutinating antigens.

IgM

Immunoglobulin Classes III. IgA u Structure: Dimer u Percentage serum antibodies: 10-15% u Location: Secretions (tears, saliva, intestine, milk), blood and lymph. u Half-life in serum: 6 days u Complement Fixation: No u Placental Transfer: No u Known Functions: Localized protection of mucosal surfaces. Provides immunity to infant digestive tract.

Secretory IgA n Exists as TWO basic structural units, a DIMER n Produced by cells lining the mucous membranes.

Secretory Igor

Immunoglobulin Classes IV. IgD u Structure: Monomer u Percentage serum antibodies: 0.2% u Location: B-cell surface, blood, and lymph u Half-life in serum: 3 days u Complement Fixation: No u Placental Transfer: No u Known Functions: In serum function is unknown. On B cell surface, initiate immune response.

Immunoglobulin Classes V. IgE u Structure: Monomer u Percentage serum antibodies: 0.002% u Location: Bound to mast cells and basophils throughout body. Blood. u Half-life in serum: 2 days u Complement Fixation: No u Placental Transfer: No u Known Functions: Allergic reactions. Possibly lysis of worms.

How Do B Cells Produce Antibodies? u B cells develop from stem cells in the bone marrow of adults (liver of fetuses). u After maturation B cells migrate to lymphoid organs (lymph node or spleen). u Clonal Selection: When a B cell encounters an antigen it recognizes, it is stimulated and divides into many clones called plasma cells, which actively secrete antibodies. u Each B cell produces antibodies that will recognize only one antigenic determinant.

Clonal Selection of B Cells is Caused by Antigenic Stimulation

Humoral Immunity (Continued) Apoptosis u Programmed cell death (“Falling away”). u Human body makes 100 million lymphocytes every day. If an equivalent number doesn’t die, will develop leukemia. u B cells that do not encounter stimulating antigen will self-destruct and send signals to phagocytes to dispose of their remains. u Many virus infected cells will undergo apoptosis, to help prevent spread of the infection.

Humoral Immunity (Continued) Clonal Selection u Clonal Selection: B cells (and T cells) that encounter stimulating antigen will proliferate into a large group of cells. u Why don’t we produce antibodies against our own antigens? We have developed tolerance to them. u Clonal Deletion: B and T cells that react against self antigens appear to be destroyed during fetal development. Process is poorly understood.

Immunological Memory Antibody Titer: The amount of antibody in the serum. Pattern of Antibody Levels During Infection Primary Response: u After initial exposure to antigen, no antibodies are found in serum for several days. u A gradual increase in titer, first of IgM and then of IgG is observed. u Most B cells become plasma cells, but some B cells become long living memory cells. u Gradual decline of antibodies follows.

Immunological Memory (Continued) Secondary Response: u Subsequent exposure to the same antigen displays a faster and more intense antibody response. u Increased antibody response is due to the existence of memory cells, which rapidly produce plasma cells upon antigen stimulation.

Antibody Response After Exposure to Antigen

Overview of the Immune Response